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EP4453554B1 - Procédé et systèmes pour l'analyse d'ions à l'aide d'une spectrométrie de mobilité différentielle et d'un guide d'ions comprenant des électrodes auxiliaires supplémentaires - Google Patents

Procédé et systèmes pour l'analyse d'ions à l'aide d'une spectrométrie de mobilité différentielle et d'un guide d'ions comprenant des électrodes auxiliaires supplémentaires

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Publication number
EP4453554B1
EP4453554B1 EP22829868.3A EP22829868A EP4453554B1 EP 4453554 B1 EP4453554 B1 EP 4453554B1 EP 22829868 A EP22829868 A EP 22829868A EP 4453554 B1 EP4453554 B1 EP 4453554B1
Authority
EP
European Patent Office
Prior art keywords
ions
ion guide
auxiliary electrodes
rods
differential mobility
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP22829868.3A
Other languages
German (de)
English (en)
Other versions
EP4453554A1 (fr
Inventor
Nicholas G. BLOOMFIELD
Igor Chernushevich
Yves Le Blanc
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
DH Technologies Development Pte Ltd
Original Assignee
DH Technologies Development Pte Ltd
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Publication of EP4453554A1 publication Critical patent/EP4453554A1/fr
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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/62—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
    • G01N27/622—Ion mobility spectrometry
    • G01N27/623—Ion mobility spectrometry combined with mass spectrometry
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/62—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
    • G01N27/622—Ion mobility spectrometry
    • G01N27/624—Differential mobility spectrometry [DMS]; Field asymmetric-waveform ion mobility spectrometry [FAIMS]
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/0027—Methods for using particle spectrometers
    • H01J49/0031—Step by step routines describing the use of the apparatus
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/004—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/06—Electron- or ion-optical arrangements
    • H01J49/062—Ion guides
    • H01J49/063—Multipole ion guides, e.g. quadrupoles, hexapoles
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/24—Vacuum systems, e.g. maintaining desired pressures

Definitions

  • Mass spectrometry is an analytical technique for measuring the mass-to-charge ratios (m/z) of molecules within a sample, with both quantitative and qualitative applications. For example, mass spectrometry can be used to identify unknown compounds in a test substance, determine the isotopic composition of elements in a specific molecule, determine the structure of a particular compound by observing its fragmentation, and/or quantify the amount of a particular compound in a test sample. MS typically involves converting the sample molecules into ions using an ion source and separating and detecting the ionized molecules with electric and/or magnetic fields due to differences in their mass-to-charge ratios (m/z) using one or more mass analyzers.
  • differential mobility spectrometry may be used on its own to analyze a sample
  • a differential mobility spectrometer may also be interfaced with a mass spectrometer to serve as a front end orthogonal separation method, thus taking advantage of the atmospheric pressure, gas phase, and continuous ion separation capabilities of differential mobility spectrometry to provide enhanced analytical power to the differential mobility spectrometry-MS system.
  • Such a differential mobility spectrometry-MS system may enhance numerous areas of sample analysis, including proteomics, peptide/protein conformation, pharmacokinetic, metabolism analysis, trace level explosives detection, and petroleum monitoring, all by way of non-limiting example.
  • the present teachings are generally directed to improved methods and systems for performing differential mobility spectrometry in combination with MS.
  • the invention is defined in method claim 1 and apparatus claim 9.
  • a user typically iteratively adjusts the COV applied (e.g., ramps stepwise) across the electrodes of the differential mobility spectrometry device to allow for transmission therethrough of different subsets of ions varying in their differential mobility across the COV range.
  • Such transmitted ions are then passed through downstream ion optics disposed in one or more vacuum chambers, where they may be subjected to further processing (e.g., mass analysis).
  • a significant pause may be conventionally provided between the application of different COV values to the differential mobility spectrometry device in order to avoid cross-talk between groups of ions transmitted at each COV value, thereby reducing the duty cycle of the analysis and reducing the number of data points that can be obtained during a given time period.
  • the sample comprises the eluent of a liquid chromatography (LC)
  • particular analytes within the sample may be eluted only during a finite window (e.g., during an LC peak).
  • LC liquid chromatography
  • a method of analyzing ions comprising receiving in an ion guide a first plurality of ions transmitted from a differential mobility spectrometry device while having a first combination of separation voltage (SV) and compensation voltage (COV) applied thereto, wherein the ion guide comprises a multipole rod set extending along a longitudinal axis from an inlet end to an outlet end and a plurality of auxiliary electrodes.
  • SV separation voltage
  • COV compensation voltage
  • a second plurality of ions may be received in the ion guide, the second plurality of ions being transmitted by the differential mobility spectrometry device while having a second combination of SV and COV applied thereto, wherein at least one of the SV and COV in the second combination differs from the SV and COV in the first combination.
  • a DC voltage may be applied to the auxiliary electrodes so as to generate an axial electric field along a longitudinal axis of the ion guide.
  • the ion guide may be operated at a range of pressures, for example, in some aspects, the ion guide may disposed within a vacuum chamber having a pressure in the millitorr (mTorr) range.
  • mTorr millitorr
  • the ion guide can be configured depending on the configuration of the differential mobility spectrometry device.
  • the differential mobility spectrometry device may be operated in an "enabled mode" as noted above in which a SV-COV combination is applied thereto such that only certain ions exhibiting a particular ion mobility (or range of ion mobilities) are transmitted through the differential mobility spectrometry device.
  • the differential mobility spectrometry device may be adjusted from "enabled mode" to operate in a "transmission mode” in which ion mobility filtering is disabled prior to the transmitted ions being received by the ion guide.
  • the differential mobility spectrometry device in transmission mode, may be operated such that substantially all ions received from an ion source are transmitted to the downstream ion guide.
  • the signals provided to the auxiliary electrodes may be adjusted depending on whether the differential mobility spectrometry device is filtering ions based on their mobilities, for example, whether the differential spectrometry device is being operated in "transmission mode” or "enabled mode.”
  • the auxiliary electrodes when the differential mobility spectrometer is operating in "transmission mode,” the auxiliary electrodes may have a signal applied thereto such that the auxiliary electrodes do not generate an axial electric field along the longitudinal axis of the ion guide.
  • the auxiliary electrodes may be operated at the offset potential of the multipole rods.
  • the signal applied to the auxiliary electrodes may be adjusted (e.g., by applying a DC voltage) such that an axial electric field is generated by the auxiliary electrodes.
  • the differential mobility spectrometry device can also be considered to essentially operate in "transmission mode" when low values of SV (e.g., less than a few hundreds of volts) and COV (e.g., less than 1V) results in no substantial separation for many of the ions generated by the source.
  • switching the differential mobility spectrometry device between transmission mode and enabled mode can include adjusting potentials applied to other elements utilized with the ion guide.
  • a lens may be disposed adjacent the outlet end of the ion guide.
  • the method may comprise adjusting a potential on the lens to be more attractive to the ions relative to an offset of the multipole rod set of the ion guide.
  • the multipole rod set of the ion guide may comprise quadrupole rod set comprising a first pair of rods and a second pair of rods, wherein the rods of the quadrupole rod set are spaced apart from the longitudinal axis such that the rods of each pair are disposed on opposed sides of the longitudinal axis.
  • the plurality of auxiliary electrodes may comprise at least a pair of auxiliary electrodes extending along the longitudinal axis on opposed sides thereof, wherein each of the auxiliary electrodes is interposed between a single rod of the first pair of rods and a single rod of the second pair of rods.
  • a mass spectrometry system comprising a differential mobility spectrometry device, wherein when activated, the differential mobility spectrometry device is configured to separate ions based on their differential mobilities.
  • the system may also comprise an ion guide configured to receive ions from the differential mobility spectrometry device, wherein the ion guide comprises a multipole rod set extending along a longitudinal axis from an inlet end to an outlet end and a plurality of auxiliary electrodes.
  • the system may also comprise a control system operatively coupled to the differential mobility spectrometry device and the ion guide, the control system configured to: cause a first combination of separation voltage (SV) and compensation voltage (COV) to be applied to the differential mobility spectrometry device so as to transmit a first plurality of ions; cause a second combination of SV and COV to be applied to the differential mobility spectrometry device so as to transmit a second plurality of ions, wherein at least one of the SV and COV in the second combination differs from the SV and COV in the second combination; and cause a DC voltage to be applied to the auxiliary electrodes while transmitting the first and second plurality of ions through the ion guide so as to generate an axial electric field along a longitudinal axis of the ion guide.
  • SV separation voltage
  • COV compensation voltage
  • a duration between terminating transmission of the first plurality of ions and initiating transmission of the second plurality of ions is less than about 30 ms.
  • the duration between terminating transmission of the first plurality of ions and initiating transmission of the second plurality of ions can be less than about 10 ms.
  • the ion guide may be disposed in a vacuum chamber having a pressure in the mTorr range.
  • control system may be further configured to cause the differential mobility spectrometry device operating in a transmission mode in which ion mobility filtering is disabled, and adjust the DC voltage applied to the auxiliary electrodes when operating in transmission mode to remove the axial electric field generated by the auxiliary electrodes.
  • control system may be configured to adjust the DC voltage applied to the auxiliary electrodes to be substantially the same as a DC offset of the multipole rods of the ion guide when operating in transmission mode.
  • the mass spectrometry system may further comprise a lens disposed adjacent the outlet end of the ion guide, wherein the control system is configured to adjust a potential on a lens such that the lens is more attractive to the ions relative to an offset of the quadrupole rod set of the ion guide.
  • the multipole rod set may comprise a quadrupole rod set.
  • the quadrupole rod set can comprise a first pair of rods and a second pair of rods and wherein the rods of the quadrupole rod set are spaced apart from the longitudinal axis such that the rods of each pair are disposed on opposed sides of the longitudinal axis.
  • the plurality of auxiliary electrodes may comprise at least one pair of auxiliary electrodes extending along the longitudinal axis on opposed sides thereof, wherein each of the auxiliary electrodes may be interposed between a single rod of the first pair of rods and a single rod of the second pair of rods.
  • the auxiliary electrodes can have a variety of configuration. For example, in some aspects, a distance between an innermost surface of the auxiliary electrodes and the longitudinal axis of the ion guide decreases along the length of the ion guide. Additionally or alternatively, the auxiliary electrodes may have a T-shaped cross-sectional shape.
  • the terms “about” and “substantially equal” refer to variations in a numerical quantity that can occur, for example, through measuring or handling procedures in the real world; through inadvertent error in these procedures; through differences in the manufacture, source, or purity of compositions or reagents; and the like.
  • the terms “about” and “substantially” as used herein mean 10% greater or lesser than the value or range of values stated or the complete condition or state. For instance, a concentration value of about 30% or substantially equal to 30% can mean a concentration between 27% and 33%.
  • the terms also refer to variations that would be recognized by one skilled in the art as being equivalent so long as such variations do not encompass known values practiced by the prior art.
  • Systems and methods in accordance with various aspects of the present teachings may be effective to improve the performance of a differential mobility spectrometry device and a MS device operating in tandem relative to conventional systems for DMS-MS.
  • a substantial pause is conventionally required between each of consecutive COVs applied to DMS electrodes across a desired COV range (e.g., a pause of ⁇ 20-30 ms)
  • methods and systems in accordance with the present teachings utilize an ion guide for receiving transmitted ions from the differential mobility spectrometry device that may significantly reduce a pause duration between the application of different COV values without substantially increasing the likelihood of contamination or cross-talk between groups of ions transmitted by the differential mobility spectrometry device at each COV value.
  • FIG. 1 schematically depicts an embodiment of an exemplary system 100 for performing differential mobility spectrometry-tandem mass spectrometry (differential mobility spectrometry-MS/MS) in accordance with various aspects of the applicant's teachings. It should be understood that mass spectrometry system 100 represents only one possible configuration and that other mass spectrometry systems modified in accordance with the present teachings can also be used as well.
  • the system 100 generally comprises a differential mobility spectrometry device 132 configured to receive ions 103 from an ion source 104 and transmit at least a portion of the ions received thereby to one or more downstream vacuum chambers (e.g., vacuum chamber 140, vacuum chamber 150) for processing (e.g., mass analyzing) in accordance with the present teachings.
  • the downstream vacuum chamber 140 houses an ion guide 142 through which ions received from the differential mobility spectrometry device 132 are transported prior to entering a second vacuum chamber 150 that may house a mass filter 152, a fragmentation device 154, and a ToF mass analyzer 156.
  • One or more power supplies may be configured to apply various DC, AC, and/or RF signals to the various components of the system 100 for controlling the movement and processing of ions 103 within the system 100, as otherwise discussed herein.
  • the exemplary second vacuum chamber 150 is depicted as housing two quadrupoles (i.e., elongated rod sets mass filter 152 (also referred to as Q1), collision cell 154 (also referred to as q2), and a ToF mass analyzer 156, it will be appreciated that more or fewer mass analyzers or ion processing elements can be included in systems in accordance with the present teachings.
  • mass filter 152 and collision cell 154 are generally referred to herein as quadrupoles (that is, they have four rods) for convenience, the elongated rod sets 152, 154 may be other suitable multipole configurations.
  • collision cell 154 can comprise a hexapole, octapole, etc.
  • the mass spectrometry system 100 can comprise any of triple quadrupoles, linear ion traps, quadrupole time of flight, Orbitrap or other Fourier transform mass spectrometry systems, all by way of non-limiting examples.
  • the differential mobility spectrometry device 132 is contained within a curtain chamber 130, which is defined by a curtain plate or boundary member 131 that contains an opening 130a in communication with an ionization chamber 110.
  • a curtain gas supply 133 is fluidly connected to the curtain chamber 130 to supply curtain gas thereto.
  • the exemplary differential mobility spectrometry device 132 comprises a pair of opposed electrode plates 134a,b that surround a transport gas that drifts from an inlet of the differential mobility spectrometry device 132 adjacent the opening 130a to an outlet of the differential mobility spectrometry device 132 adjacent inlet 140b of the vacuum chamber 140 containing the ion guide 142.
  • the pressure of the curtain gases in the curtain chamber 130 can provide both a curtain gas outflow out of the opening 130a, as well as a curtain gas inflow into the inlet of the differential mobility spectrometry device 132, which inflow becomes the drift gas that carries the ions 103 through the analytical gap 136 toward the inlet 140b of the vacuum chamber 140 (e.g., an orifice in plate 140a).
  • a voltage can be applied to the curtain plate 131 from a suitable source to propel the ions 103 across the gap between the curtain plate 131 and the inlet end of the electrodes 134a,b.
  • the ions 103 Upon entering the analytical gap 136, the ions 103 are swept along in the drift gas, and while being subjected to varying electric field generated by the parallel electrodes 134a,b to cause separation of ions based on ion mobility properties. Selected ions 103 (e.g., ions not neutralized on the electrodes 134a,b) and drift gas continue to travel down the analytical gap 132 toward inlet 140b of the vacuum chamber 140, within which the transmitted ions may be subjected to further processing.
  • Selected ions 103 e.g., ions not neutralized on the electrodes 134a,b
  • drift gas continue to travel down the analytical gap 132 toward inlet 140b of the vacuum chamber 140, within which the transmitted ions may be subjected to further processing.
  • a separation voltage (SV) and a compensation voltage (COV) can be applied to the differential mobility spectrometry device 132, when enabled, so as to perform differential mobility separation on the ions within the drift gas flowing through the analytical gap 136 between the parallel plate electrodes 134a,b.
  • SV separation voltage
  • COV compensation voltage
  • the SV may be an RF voltage signal applied to the electrodes 134a,b so as to generate an electric force across the analytical gap 136 (e.g., perpendicular to the central axis of the analytical gap 136) such that ions of various species migrate radially away from the axis of the transport chamber by a respective characteristic amount during each cycle of the RF waveform due to differences in their respective mobilities during the high field and low field portions of the RF signal.
  • the COV which may be a DC potential applied across the analytical gap 136, can provide a counterbalancing electrostatic force to that of the SV. In this manner, the COV can be tuned so as to preferentially restore a stable trajectory to particular ions such that they will traverse the entire length of the analytical gap 136 and be transmitted through inlet 140b.
  • the SV-COV combination may be adjusted in a variety of manners such that one or more species of ions may be transmitted from the differential mobility spectrometry device 132 into the inlet 140b as their drift therethrough does not cause them to be neutralized at the electrodes 134a,b.
  • the SV can be fixed at a value while the COV is adjusted (e.g., scanned) to serially pass ions exhibiting a particular differential mobility so as to generate a mobility spectrum.
  • a mobility spectrum may be generated by setting the COV to a fixed value while the SV is scanned so as to serially pass ions of interest.
  • the differential mobility spectrometry device 132 may be operated with both the COV and SV fixed such that only ion species with a particular differential mobility are transmitted through from the differential mobility spectrometry device 132 while the remaining species of ions drift toward the electrodes 134a,b and are neutralized.
  • Examples of differential mobility spectrometers which may be modified for use in accordance with the present teachings are described, for example, in U.S. Patent Nos. 8,084,736 and 9,835,588 , the teachings of which are hereby incorporated by reference in their entireties.
  • the computer system 180 may cause the differential mobility spectrometry device 132 to alternatively operate in a mode in which the differential mobility spectrometry device 132 is configured to not filter and/or not separate ions based on their differential mobilities (e.g., substantially all ions received from the ion source 104 are configured to be transmitted therethrough without being neutralized on the plates 134a,b).
  • DC voltages applied to the electrode plates 134a,b may alternatively represent a symmetric non-zero offset value of the same polarity to the ions of interest so as to generate a substantially radially-inward force (e.g., toward the central axis) on the ions as they are transmitted between the electrode plates 134a,b.
  • differential mobility spectrometry device can also be considered to essentially operate in transmission mode when low values of SV (e.g., less than a few hundreds of volts) and COV (e.g., less than 1V) results in no substantial separation for many of the ions received from the ion source 104.
  • SV e.g., less than a few hundreds of volts
  • COV e.g., less than 1V
  • the differential mobility spectrometry device 132 depicted in FIG. 1 is just one example of a device suitable for filtering ions based on their ion mobility characteristics, and that other differential mobility spectrometry device configurations are suitable for use in accordance with the present teachings.
  • the device 132 of FIG. 1 defines a straight ion path extending between parallel plates 134a,b
  • suitable differential mobility spectrometry devices may alternatively provide a curved ion path between an outer electrode and an inner electrode, the space between defining the analytical gap.
  • an asymmetric dispersion voltage or separation voltage is applied to the inner electrode, with the curved ion path providing a focusing effect in the presence of the asymmetric waveform that guides ions around the inner electrode within the analytical gap.
  • a compensation voltage can be applied to the outer electrode to select for specific ions having specific asymmetric differential ion mobility properties.
  • both the asymmetric dispersion voltage and compensation voltage may be set to 0V.
  • the curtain gas can be set to flow rates determined by a flow controller and valves so as to alter the drift time of ions within the differential mobility spectrometry device 132.
  • a throttle gas supply (not shown) can provide a throttle gas to the outlet end of the differential mobility spectrometry device 132 so as to modify the flow rate of the drift gas through the differential mobility spectrometry device 132 as described, for example, in U.S. Patent Nos. 8,084,736 , 8,513,600 , and 9,171,711 , all of which are incorporated herein by reference.
  • Each of the curtain gas supply 133 and throttle gas supply can provide the same or different pure or mixed composition gas to the curtain gas chamber.
  • the curtain gas can be air, O 2 , He, N 2 , or CO 2 .
  • the pressure of the curtain chamber 130 can be maintained, for example, at or near atmospheric pressure (i.e., 760 Torr).
  • the system 100 can include a chemical modifier supply (not shown) for supplying a chemical modifier and/or reagent (hereinafter referred as chemical modifier) to the curtain and throttle gases.
  • the modifier supply can be a reservoir of a solid, liquid, or gas through which the curtain gas is delivered to the curtain chamber 130.
  • the curtain gas can be bubbled through a liquid modifier supply.
  • a modifier liquid or gas can be metered into the curtain gas, for example, through an LC pump, syringe pump, or other dispensing device for dispensing the modifier into the curtain gas at a known rate.
  • the modifier can be introduced using a pump so as to provide a selected concentration of the modifier in the curtain gas.
  • the modifier supply can provide any modifier known in the art including, by way of non-limiting example, water, volatile liquid (e.g., methanol, propanol, acetonitrile, ethanol, acetone, and benzene), including alcohols, alkanes, alkenes, halogenated alkanes and alkenes, furans, esters, ethers, aromatic compounds.
  • the chemical modifier can interact with the ions 103 such that the ions differentially interact with the modifier (e.g., cluster via hydrogen or ionic bonding) during the high and low field portions of the SV, thereby effecting the COV needed to counterbalance a given SV. In some cases, this can increase the separation between the ion species.
  • the modifier e.g., cluster via hydrogen or ionic bonding
  • the ions 103 emitted into the curtain chamber 130 via curtain chamber inlet 130a can be generated by any known or hereafter developed ion source for generating ions and modified in accordance with the present teachings.
  • ion sources suitable for use with the present teachings include atmospheric pressure chemical ionization (APCI) sources, electrospray ionization (ESI) sources, continuous ion source, a pulsed ion source, an inductively coupled plasma (ICP) ion source, a matrix-assisted laser desorption/ionization (MALDI) ion source, a glow discharge ion source, an electron impact ion source, a chemical ionization source, or a photo-ionization ion source, among others.
  • APCI atmospheric pressure chemical ionization
  • ESI electrospray ionization
  • continuous ion source continuous ion source
  • ICP inductively coupled plasma
  • MALDI matrix-assisted laser desorption/ionization
  • the ion source 104 comprises an electrospray electrode, which can comprise a capillary fluidly coupled to a sample source 102 (e.g., through one or more conduits, channels, tubing, pipes, capillary tubes, etc.), and which terminates in an outlet end that at least partially extends into the ionization chamber 110 to discharge the liquid sample therein.
  • a sample source 102 e.g., through one or more conduits, channels, tubing, pipes, capillary tubes, etc.
  • the outlet end of the electrospray electrode can atomize, aerosolize, nebulize, or otherwise discharge (e.g., spray with a nozzle) the liquid sample into the ionization chamber 110 to form a sample plume comprising a plurality of micro-droplets generally directed toward (e.g., in the vicinity of) the curtain plate opening 130a.
  • analytes contained within the micro-droplets can be ionized (i.e., charged) by the ion source 104, for example, as the sample plume is generated.
  • the outlet end of the electrospray electrode can be made of a conductive material and electrically coupled to a pole of a voltage source (not shown), while the other pole of the voltage source can be grounded.
  • Micro-droplets contained within the sample plume can thus be charged by the voltage applied to the outlet end such that as the desorption solvent within the droplets evaporates during desolvation in the ionization chamber 110 such bare charged analyte ions are released and drawn toward the curtain plate opening 130a.
  • One or more power supplies can supply power to the ion source 104 with appropriate voltages for ionizing the analytes in either positive ion mode (analytes in the sample are protonated, generally forming cations to be analyzed) or negative ion mode (analytes in the sample are deprotonated, generally forming anions to be analyzed).
  • the ion source 104 can be nebulizer-assisted or non-nebulizer assisted.
  • ionization can also be promoted with the use of a heater (not shown), for example, to heat the ionization chamber so as to promote dissolution of the liquid discharged from the ion source.
  • the system 100 can include a sample source 102 configured to provide a sample to the ion source 104.
  • the sample source 102 can be any suitable sample inlet system known in the art.
  • the ion source 102 can be configured to receive a fluid sample from a variety of sample sources, including a reservoir containing a fluid sample that is delivered to the sample source (e.g., pumped) or via an injection of a sample into a carrier liquid.
  • the sample source 102 may be a sample separation device utilizing techniques such as, but not limited to, liquid chromatography (LC), gas chromatography, or capillary electrophoresis.
  • LC liquid chromatography
  • gas chromatography gas chromatography
  • capillary electrophoresis capillary electrophoresis
  • the sample separation device may comprise an in-line liquid chromatography (LC) column, for example, that is configured to separate one or more compounds from a sample over time.
  • the sample to be analyzed may be the eluent of the LC column, whose composition (and the analytes contained therein) may change over time, for example, based on binding affinity and/or the elution gradient applied to the LC column.
  • ions exiting the differential mobility spectrometry device 132 may enter the vacuum chamber 140 via inlet 140b containing the ion guide 142. It will be appreciated, however, that one or more intermediate vacuum chambers (not shown) may be disposed between the outlet of the differential mobility spectrometry device 132 and the vacuum chamber 140.
  • Such intermediate vacuum chambers may be maintained at elevated pressures greater than the vacuum chamber 140 within which the ion guide 142 is disposed, and may contain one or more RF ion guides (e.g., quadrupoles, QJet) and/or ion optical elements that utilize a combination of gas dynamics and radio frequency fields to enable the efficient transport of ions transfer ions downstream to the increasingly lower pressure vacuum chambers.
  • RF ion guides e.g., quadrupoles, QJet
  • Each of these RF ion guides can be configured to focus ions while enabling transport through one or more differential vacuum regions.
  • the ionization chamber 110 and curtain chamber 130 may be maintained at atmospheric or substantially atmospheric pressure (e.g., about 760 Torr), while the vacuum chamber 140 within which the ion guide 142 is housed, can be associated with a pump (not shown, e.g., a turbomolecular pump) operable to evacuate the chamber to a pressure suitable to provide collisional cooling within the ion guide 142.
  • a pump not shown, e.g., a turbomolecular pump
  • the vacuum chamber 140 can be evacuated to a pressure approximately in the range of about 1 mTorr to about 30 mTorr, though other pressures can be used for this or for other purposes.
  • the ion guide 142 may generally include a quadrupole rod set 144 comprising four rods surrounding and parallel to the longitudinal axis along which the ions are transmitted.
  • the application of various RF and/or DC potentials to the quadrupole rod set 144 of the ion guide 142 may provide collisional cooling of the ions (e.g., in conjunction with the pressure of vacuum chamber 140) and/or help form an ion beam prior to delivering ions into the vacuum chamber 150 through the exit aperture 150b in lens 150a (e.g., an orifice plate, IQ1), which is disposed between the vacuum chamber 140 of ion guide 142 and the adjacent vacuum chamber 150.
  • lens 150a e.g., an orifice plate, IQ1
  • the controller 180 may cause the ion guide 142 to operate in a first mode in which the ion guide 142 provides collisional cooling and/or radial focusing without providing an axial electric field as discussed otherwise herein.
  • electric potentials applied to the auxiliary electrodes 146 may be adjusted such that an axial electric field is generated within the ion guide 142 so as to reduce the transit time of the ions therethrough.
  • the filtering of ions by the differential mobility spectrometry device 132 may, in some instances, sufficiently reduce ion flux through the downstream elements (e.g., by filtering the ions 103 received from the ion source 104 based on their differential mobility) to effect space charge conditions within ion guide 142, which when present may be effective to help accelerate ions through ion guide 142 toward the downstream vacuum chamber.
  • space charge conditions e.g., when the differential mobility spectrometry device 132 is in "enabled mode
  • ion transit through ion guide 142 may be slowed.
  • the use of a substantial delay as in conventional devices may provide additional time to ensure optimum ion transmission from the ion guide, such conventional methods significantly increase the duty cycle for each SV-COV combination applied by the differential mobility spectrometry device 132.
  • the provision of an additional axial electric field by the auxiliary electrodes when the differential mobility spectrometry device 132 is operating in enabled mode reduces the ion transit time through the ion guide 142 such that a pause between the application of different SV-COV combinations can be reduced relative to conventional systems without substantially increasing the likelihood of contamination or cross-talk between groups of ions transmitted by the differential mobility spectrometry device 132.
  • the electric field created by the auxiliary electrodes may be preferably applied only when the differential mobility spectrometry device is operating in enabled mode due to ion transmission control within the ion guide 142 (e.g., when being operated as a conventional quadrupole ion guide) behaving in a less than ideal manner (e.g., non-linear) .
  • the auxiliary electrodes 146 may be effective to generate an axial electric field within ion guide 142 in a variety of manners.
  • an example ion guide 242 comprising a quadrupole rod set 244 and a plurality of auxiliary electrodes 246 in accordance with various aspects of the present teachings is depicted.
  • the quadrupole rod set 244 consists of four parallel rod electrodes 244a-d that are disposed around and parallel to a central longitudinal axis (Z) extending from an input end (e.g., toward ion source 102 in FIG. 1 ) to an outlet end (e.g., toward vacuum chamber 150).
  • the rods 244a-d have a cylindrical shape (i.e., a circular cross-section) with the innermost surface of each rod 244a-d disposed equidistant from the central axis (Z) and with each of the rods 244a-d being equivalent in size and shape to one another.
  • the rods 244a-d are generally grouped into two pairs of rods (e.g., a first pair comprising rods 244a,c disposed on the X-axis and a second pair comprising rods 244b,d disposed on the Y-axis), with rods of each pair being disposed on opposed sides of the central axis (Z) and to which identical electrical signals can be applied.
  • the minimum distance between each of the rods 244a-d and the central axis (Z) is defined by a distance r 0 such that the innermost surface of each rod 244a-d is separated from the innermost surface of the other rod in its rod pair across the central longitudinal axis (Z) by a minimum distance of 2 r 0 . It will be appreciated that though the rods 244a-d are depicted as cylindrical, the cross-sectional shape, size, and/or relative spacing of the rods 244a-d may be varied as is known in the art.
  • the rods 244a-d are electrically conductive (i.e., they can be made of any conductive material such as a metal or alloy) and can be coupled to one or more power supplies such that one or more electrical signals can be applied to each rod 244a-d alone or in combination.
  • RF radiofrequency
  • the power system can apply an electric potential to the first pair of rods 244a,c of a rod offset voltage (RO) - Vcos ⁇ t, where V is the zero-to-peak amplitude of the RF signal provided by an RF voltage source, ⁇ is the angular frequency of the RF signal, and t is time.
  • the power system can also apply an electric signal to the second pair of rods 244b,d of RO + Vcos ⁇ t such that the RF electrical signals applied to the first pair of rods 244a,c and the second pair of rods 244b,d are 180° out of phase with one another.
  • RO rod offset voltage
  • ion guides in accordance with various aspects of the present teaching additionally include a plurality of auxiliary electrodes, which as shown in FIGS. 2A-B may comprise a plurality of linear accelerator (LINAC) electrodes 246a-d.
  • the auxiliary electrodes are electrically conductive (i.e., they can be made of any conductive material such as a metal or alloy) and can be coupled to one or more power supplies such that one or more electrical signals can be applied to each auxiliary electrode 246a-d alone or in combination.
  • auxiliary electrodes 2A-B includes four auxiliary electrodes interposed between rods 244a-d of the quadrupole rod set 244, more or fewer auxiliary electrodes can be utilized in accordance with the present teachings.
  • the plurality of auxiliary electrodes may just include a pair of electrodes 246a,c disposed on opposed sides of the longitudinal axis for generating an axial electric field in accordance with the present teachings.
  • these LINAC electrodes 246a-d are disposed within a region (e.g., vacuum chamber 140 of FIG. 1 ) that is maintained at a pressure in a range from about 5 to about 15 mTorr.
  • the auxiliary electrodes 246a-d extend along the longitudinal axis (Z) between the input end ( FIG. 2A ) and the output end ( FIG. 2B ) of the quadrupole rod set 244.
  • the auxiliary electrodes 246a-d comprise four T-shaped electrodes that are each disposed between a single rod of the first pair of rods 244a,c and a single rod of the second pair of rods 244b,d. Comparing FIG.
  • the radial portion of the auxiliary electrodes 246a-d tapers along the length of the quadrupole rod set 244 such that the innermost surface of the auxiliary electrodes 246a-d adjacent to the input end ( FIG. 2A ) is separated from the longitudinal axis by a larger distance than the innermost surface of the auxiliary electrodes 246a-d adjacent to the output end ( FIG. 2B ).
  • this tapering may establish an electric field component along the axis (Z) that helps axially transport (e.g., accelerate) ions from the input end to the output end of the ion guide 242.
  • the ion guide 142 is generally configured to transmit ions received from the differential mobility spectrometry device 132 for further processing within downstream high-vacuum chamber 150.
  • the provision of RF signals and a DC rod offset (RO) to the quadrupole rod set 244 as well as the relatively high pressures within ion guide 242 may provide collisional cooling and/or be effective to radially focus the ions into an ion beam prior to delivering ions into a lower pressure region (e.g., the vacuum chamber 150 of FIG. 1 ).
  • a lower pressure region e.g., the vacuum chamber 150 of FIG. 1
  • a controller e.g., controller 180 of FIG. 1
  • a controller can additionally cause a DC power supply (not shown) to apply an additional DC voltage to the auxiliary electrodes that can be effective to superimpose an electric field having a component in the longitudinal direction of the quadrupole rod set 244 (along the z-direction) to accelerate the ions toward the outlet end of the ion guide 242.
  • the amplitude of the superimposed electric field can increase as a function of decreasing radial distance of the auxiliary electrodes 246 from the longitudinal axis, thereby causing the ions to be accelerated toward the outlet end of the ion guide 142.
  • the controller causes a DC signal to be applied to the auxiliary electrodes 246 equal to the RO of quadrupole rod set 244
  • the auxiliary electrodes 246 would not be effective to generate an axial electric field as the electric potential at each point along the longitudinal axis of the ion guide 242 is substantially constant (RO).
  • auxiliary electrodes 246a-d are depicted in FIGS. 2A-B as having a T-shaped cross-section, the cross-sectional shape, size, and/or relative spacing of the auxiliary electrodes may be varied to provide an axial electric field within a multipole ion guide in accordance with various aspects the present teachings.
  • FIGS. 3A-B another example ion guide 342 in accordance with the present teachings is depicted.
  • the ion guide 342 is similar to ion guide 242, but differs in that the auxiliary electrodes 346a-d instead comprise four rods having a circular cross-sectional shape. Comparing FIG.
  • rods 346a-d are tilted (e.g., non-parallel relative to the central axis) such that the innermost surface of the electrodes 346a-d are closer to the axis (Z) at the output end of the ion guide 342.
  • multipole ion guide 242 ( FIGS. 2A-B ) and multipole ion guide 342 ( FIGS. 3A-B ) are depicted as each comprising four rods (i.e., 244a-d, 344a-d), the present teachings are not so limited to quadrupole rod sets. Rather, multipole ion guides in accordance with the present teachings can comprise other suitable multipole configurations for providing collisional cooling of the ions and/or helping form an ion beam prior to delivering ions into a downstream vacuum chamber such as hexapole, octapole, decapole, dodecapole, and other higher-order multipoles.
  • FIGS. 2A-B and 3A-B another example of an ion guide 442 in accordance with the present teachings is depicted.
  • the ion guide 442 differs from that of FIGS. 2A-B and 3A-B in that the ion guide 442 comprises a higher order multipole, in this example, an octapole containing eight rods 444a-h forming an octapole rod set 444 for radially confining ions as they pass through the ion guide 442.
  • RF voltages with 180-degree phase difference may be applied to the various rods of the multipole rod set.
  • the rod set that is applied with the RF voltage with the 0-degree phase is often referred to as the first pole electrode set
  • the rod electrode set that is applied with the RF voltage with about 180-degree phase relative to the first RF voltage is often referred to as the second pole electrode set.
  • rods 444a,c,e,g may be understood to be the first pole electrode set
  • rods 444b,d,f,h may be the second pole electrode set.
  • auxiliary electrodes 446 interspersed between each of the rods 444a-h forming the octapole rod set 444.
  • the auxiliary electrodes 446 of FIGS. 4A-B are in the form of rods having a circular cross-sectional shape.
  • the auxiliary electrodes 446 are tilted (e.g., non-parallel relative to the central axis) such that the innermost surface of the rods 446 at the input end of the ion guide 442 ( FIG.
  • auxiliary electrodes 446 are spaced further from the axis (Z) than the innermost surface of the rods 446 at the output end of the ion guide 442 ( FIG. 4B ) so as to generate an axial field within the ion guide 442 when an attractive DC potential is applied to the auxiliary electrodes 446 as otherwise discussed herein.
  • the depicted auxiliary electrodes 446 are in the form of cylindrical rods, a variety of configurations of auxiliary electrodes may be used to generate the axial electric field in accordance with the present teachings.
  • the cylindrical auxiliary electrodes 446 could instead auxiliary electrodes having a T-shaped cross-sectional shape as in FIGS. 2A-B , wherein the radial portions of the T-shaped electrodes tape along the length of the octapole rod set 444.
  • ions that are transmitted from the ion guide 142 enter the vacuum chamber 150 via inlet 150b of the exit lens 150a (IQ1) disposed in proximity of the output end of the ion guide 142.
  • a DC voltage may be applied to the exit lens 150a to cause the generation of an electric field that facilitates the exit of the ions from the ion guide 142.
  • a DC voltage source (not shown), operating under the control of the controller 180, can apply DC voltages to the exit lens 150a (e.g., in range of about 1 to 50 V attractive relative to the DC offset applied to the quadrupole rod set 144).
  • the exit lens 150a may be coupled to a RF power supply such that an RF signal may be applied thereto.
  • a RF voltage source operating under the control of controller 180, can apply an RF signal to exit lens 150a.
  • the lens 150a can be implemented in a variety of different ways.
  • the lenses can be in the form of a plate having an opening through which the ions pass.
  • at least one (or both) of the lenses can be implemented as a mesh.
  • the mass filter 152 can be operated as a conventional transmission RF/DC quadrupole mass filter that can be operated to select an ion of interest and/or a range of ions of interest.
  • the computer system 180 can cause suitable RF/DC voltages to be applied to the mass filter 152 so as to operate in a mass-resolving mode.
  • mass filter 152 parameters for an applied RF and DC voltage can be selected so that mass filter 152 establishes a transmission window of chosen m/z ratios, such that these ions can traverse Q1 largely unperturbed. Ions having m/z ratios falling outside the window, however, do not attain stable trajectories within the quadrupole and can be prevented from traversing the mass filter 152. It should be appreciated that this mode of operation is but one possible mode of operation for mass filter 152.
  • one or more ion optical elements (not shown) between the mass filter 152 and the fragmentation device 154 can be maintained at a much higher offset potential than mass filter 152 such that Q1 can be operated as an ion trap.
  • the potential applied to the ion optical elements (not shown) can be selectively lowered (e.g., mass selectively scanned) such that ions trapped in mass filter 152 can be accelerated into fragmentation device 154, which could also be operated as an ion trap, for example.
  • Ions transmitted by the mass filter 152 enter into the adjacent fragmentation device 154, which can be disposed in a pressurized compartment and can be configured to operate as a collision cell at a pressure approximately in the range of from about 1 mTorr to about 10 mTorr, though other pressures can be used for this or for other purposes.
  • a suitable collision gas e.g., nitrogen, argon, helium, etc.
  • a gas inlet not shown to thermalize and/or fragment ions within the ion beam.
  • the mass filter 152 when in MS/MS mode, can be operated to transmit to fragmentation device 154 precursor ions exhibiting a selected range of m/z for fragmentation into product ions within fragmentation device 154.
  • MS mode a person skilled in the art will appreciate that the parameters for RF and DC voltages applied to rods of the fragmentation device 154 can be selected so that the fragmentation device 154 transmits these ions therethrough largely unperturbed.
  • time-of-flight mass analyzer 156 can again be operated at a decreased operating pressure relative to that of fragmentation device 154, for example, less than about 1 ⁇ 10 -4 Torr (e.g., about 5 ⁇ 10 -5 Torr), though other pressures can be used for this or for other purposes.
  • time-of-flight mass analyzer 156 can be operated so as to generate ion detection signals indicative of the m/z of the precursor and/or product ions received from fragmentation device 154 based on the time required for an ion to traverse a known distance.
  • time-of-flight mass analyzer 156 is depicted as an time-of-flight device in which ions received from the fragmentation device 154 are orthogonally accelerated by a pusher plate 156a toward an ion mirror 156b, which reverses the ions' trajectory toward the detector 156c, any known or hereafter developed time-of-flight mass analyzer may be configured for use in systems according to the present teachings.
  • the mass analyzer 156 may be any of time-of-flight device, a quadrupole, an ion trap, a linear ion trap, an orbitrap, a magnetic four-sector mass analyzer, a hybrid quadrupole time-of-flight (Q-TOF) mass analyzer, or a Fourier transform mass analyzer, all by way of non-limiting example.
  • a quadrupole mass analyzer can be operated as an ion trap for trapping ions received from the fragmentation device 154, with the potentials applied to exit ion optical elements being selectively lowered such that trapped ions can be transmitted in a mass-selective manner to a detector for generating ion detection signals in response to the incident ions.
  • the computer system 180 which may be in communication with the time-of-flight mass analyzer 156 as shown in FIG. 1 , may receive and process the ion detection signals to generate a mass spectrum of ions, for example, indicating the amount of ions (e.g., intensity, count) of each m/z.
  • the system 500 of FIGS. 5A-B generally comprises a differential mobility spectrometry device 532, an ion guide 542 (Q0) having a quadrupole rod set 544 and auxiliary electrodes 546, an exit lens 550a (IQ1), a mass filter 552 (Q1), and a collision cell 554 (q2).
  • IQ1 quadrupole rod set 544 and auxiliary electrodes 546
  • Q1 quadrupole rod set 544 and auxiliary electrodes 546
  • IQ1 exit lens
  • Q1 mass filter 552
  • Q2 collision cell 554
  • a detector and/or ToF mass analyzer may be included downstream of the collision cell 554, but is not shown in FIGS. 5A-B for clarity.
  • the example system 500 includes a first set of stubby rods 551a (ST1) disposed between the lens 550a and the mass filter 552 (Q1) and a second set of RF-only stubby rods 551b (ST2) between the mass filter 552 (Q1) and collision cell 554 (q2).
  • a controller e.g., controller 180 of FIG. 1
  • the system 500 is schematically depicted in a first configuration in which the differential mobility spectrometry device 532 is operated in transmission mode.
  • the ion source is configured to generate positive ions.
  • the quadrupole rods of the collision cell 554 are maintained at a rod offset voltage of +31.2 V (RO2), with quadrupole rod set 544 of ion guide 542 (Q0) being maintained so as to provide 10 eV of collision energy to ions received thereby.
  • the quadrupole rods of rod set 544 (Q0) are maintained at +41V (RO2 + 10 eV).
  • the DC voltage applied to the auxiliary electrodes 546 may be identical to that of the offset of the quadrupole rods 544.
  • the auxiliary electrodes 546 would not be effective to generate an axial electric field as indicated by the constant electric potential along the length of the ion guide 542 on the plot below, which is intended to illustrate by way of non-limiting example relative voltages along the axis of the mass spectrometer system 500.
  • the exit lens 550a (IQ1) and first stubby rods 551a (ST1) may be maintained at a slightly more attractive voltage relative to the rod offset of quadrupole rods 544 (e.g., -2V offset).
  • the exit lens 550b and stubby rods 551a may be controlled to exhibit a DC offset of +39V such that the positive ions are transmitted downstream due to their kinetic energy and the decreased potential of exit lens 550a and stubby rods 551a relative to that of the ion guide 544.
  • the quadrupole rods are maintained at an offset as a function of the offset applied to ion guide 542 and IE1, which is the difference in potential between Q0 and RO1. Whereas IE1 is typically about 2 eV, the quadrupole rods of mass filter 552 are also maintained at +39V (RO1) in the example schematic of this configuration.
  • one or more additional ion guides may be present to transport ions from region to region (e.g., from the differential mobility spectrometry device 532 to ion guide 542 (Q0)).
  • the system 500 is schematically depicted in a second configuration in which the differential mobility spectrometry device 532 is instead enabled to filter the ions received from the ion source based on their ion mobility characteristics.
  • the differential mobility spectrometry device 532 may be configured to iteratively apply different SV-COV combinations such that only a subset of ions may be transmitted into the ion guide 542 at each SV-COV combination.
  • the DC offset of quadrupole rods 544, mass filter 552, and collision cell 554 are maintained at the same voltages as in the first configuration of FIG.
  • the DC potentials applied to the auxiliary electrodes 546 and/or the exit lens 550a may be adjusted (e.g., automatically under the control of a controller and/or as selected by the user) such that ions received by the ion guide 542 are accelerated therethrough.
  • the differential mobility spectrometry device 532 is now filtering the ions received from the ion source based on their differential mobilities in FIG. 5B , one would expect the ion flux within ion guide 542 to be lower relative to that of FIG. 5A .
  • ion guides in accordance with various aspects of the present teachings may beneficially mitigate the slower transit times (e.g., due to decreased space charge effect) to thereby improve the duty cycle and/or reduce cross talk contamination between groups of ions iteratively transmitted into the ion guide 542 at different SV-COV combinations.
  • a controller can cause the auxiliary electrodes 546 to be maintained at an attractive voltage (-41V) for the positive ions relative to that of the quadrupole rod set 544 such that an axial potential is generated along the axis as indicated in the potential plot at the bottom of FIG. 5B .
  • auxiliary electrode voltages to lower values can increase the effective axial potential generated along the axis and can be beneficial in some applications.
  • FIG. 5B depicts that the potential applied to the exit lens 550a can be adjusted relative to that of the first configuration of FIG. 5A .
  • the potential applied to the exit lens 550a (IQ1) has been adjusted to be more attractive to the example positive ions (e.g., +36V, +25V) relative to the offset applied to quadrupole rod set 544 (i.e., +41V) and relative to the offset applied to the stubby rods 551a (e.g., +39V).
  • the configuration of FIG. 5B allows ions to be initially accelerated through the ion guide 542.
  • the potential of the stubby rods 551a may be adjusted to ensure transmission of ions.
  • FIG. 6 is a block diagram that illustrates a computer system 680, upon which embodiments of the present teachings may be implemented.
  • Computer system 680 includes a bus 681 or other communication mechanism for communicating information, and a processor 682 coupled with bus 681 for processing information.
  • Computer system 680 also includes a memory 683, which can be a random access memory (RAM) or other dynamic storage device, coupled to bus 681 for storing instructions to be executed by processor 682.
  • Memory 683 also may be used for storing temporary variables or other intermediate information during execution of instructions to be executed by processor 682.
  • Computer system 680 further includes a read only memory (ROM) 684 or other static storage device coupled to bus 681 for storing static information and instructions for processor 682.
  • ROM read only memory
  • a storage device 685 such as a magnetic disk or optical disk, is provided and coupled to bus 681 for storing information and instructions.
  • Computer system 680 may be coupled via bus 681 to a display 686, such as a cathode ray tube (CRT) or liquid crystal display (LCD), for displaying information to a computer user.
  • a display 686 such as a cathode ray tube (CRT) or liquid crystal display (LCD)
  • An input device 687 is coupled to bus 681 for communicating information and command selections to processor 682.
  • cursor control 688 is Another type of user input device, such as a mouse, a trackball or cursor direction keys for communicating direction information and command selections to processor 682 and for controlling cursor movement on display 686.
  • This input device typically has two degrees of freedom in two axes, a first axis (i.e., x) and a second axis (i.e., y), that allows the device to specify positions in a plane.
  • a computer system 680 can perform the present teachings. Consistent with certain implementations of the present teachings, results are provided by computer system 680 in response to processor 682 executing one or more sequences of one or more instructions contained in memory 683. Such instructions may be read into memory 683 from another computer-readable medium, such as storage device 685. Execution of the sequences of instructions contained in memory 683 causes processor 682 to perform the process described herein. Alternatively, hard-wired circuitry may be used in place of or in combination with software instructions to implement the present teachings. Thus, implementations of the present teachings are not limited to any specific combination of hardware circuitry and software.
  • the present teachings may be performed by a system that includes one or more distinct software modules for perform a method for analyzing ions in accordance with various embodiments (e.g., a differential mobility spectrometry module, an ion guide module, a mass filter module, a fragmentation module, an analyzer module).
  • a differential mobility spectrometry module e.g., a differential mobility spectrometry module, an ion guide module, a mass filter module, a fragmentation module, an analyzer module.
  • computer system 680 can be connected to one or more other computer systems, like computer system 680, across a network to form a networked system.
  • the network can include a private network or a public network such as the Internet.
  • one or more computer systems can store and serve the data to other computer systems.
  • the one or more computer systems that store and serve the data can be referred to as servers or the cloud, in a cloud computing scenario.
  • the one or more computer systems can include one or more web servers, for example.
  • the other computer systems that send and receive data to and from the servers or the cloud can be referred to as client or cloud devices, for example.
  • Non-volatile media includes, for example, optical or magnetic disks, such as storage device 685.
  • Volatile media includes dynamic memory, such as memory 683.
  • Transmission media includes coaxial cables, copper wire, and fiber optics, including the wires that comprise bus 681.
  • Computer-readable media or computer program products include, for example, a floppy disk, a flexible disk, hard disk, magnetic tape, or any other magnetic medium, a CD-ROM, digital video disc (DVD), a Blu-ray Disc, any other optical medium, a thumb drive, a memory card, a RAM, PROM, and EPROM, a FLASH-EPROM, any other memory chip or cartridge, or any other tangible medium from which a computer can read.
  • Various forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to processor 682 for execution.
  • the instructions may initially be carried on the magnetic disk of a remote computer.
  • the remote computer can load the instructions into its dynamic memory and send the instructions over a telephone line using a modem.
  • a modem local to computer system 680 can receive the data on the telephone line and use an infra-red transmitter to convert the data to an infra-red signal.
  • An infra-red detector coupled to bus 681 can receive the data carried in the infra-red signal and place the data on bus 681.
  • Bus 681 carries the data to memory 683, from which processor 682 retrieves and executes the instructions.
  • the instructions received by memory 683 may optionally be stored on storage device 685 either before or after execution by processor 582.

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Claims (15)

  1. Procédé pour l'analyse d'ions comprenant :
    la réception, dans un guide (142, 242) d'ions, d'une première pluralité d'ions transmis depuis un dispositif de spectrométrie de mobilité différentielle (132) tout en ayant une première combinaison de tension de séparation et de tension de compensation appliquée à celui-ci, dans lequel le guide d'ions comprend un ensemble de tiges multipolaires (144) s'étendant le long d'un axe longitudinal depuis une extrémité d'entrée (140b) jusqu'à une extrémité de sortie (150b) ; et
    la réception, dans le guide d'ions, d'une seconde pluralité d'ions transmis par le dispositif de spectrométrie de mobilité différentielle tout en ayant une seconde combinaison de tension de séparation et de tension de compensation appliquée à celui-ci, dans lequel au moins l'une parmi la tension de séparation et la tension de compensation de la seconde combinaison diffère de la tension de séparation et de la tension de compensation de la première combinaison ;
    caractérisé en ce que :
    le guide d'ions comprend en outre une pluralité d'électrodes auxiliaires (246a-d) ; et
    le procédé comprend en outre, tout en transmettant la première et la seconde pluralité d'ions à travers le guide d'ions, l'application d'une tension CC aux électrodes auxiliaires de manière à générer un champ électrique axial le long d'un axe longitudinal du guide d'ions.
  2. Procédé selon la revendication 1, dans lequel une durée entre la fin de la transmission de la première pluralité d'ions et l'initiation de la transmission de la seconde pluralité d'ions est inférieure à environ 30 ms, facultativement inférieure à environ 10 ms.
  3. Procédé selon la revendication 1 ou la revendication 2, dans lequel le guide d'ions est disposé dans une chambre à vide ayant une pression dans la plage des mTorr.
  4. Procédé selon l'une quelconque des revendications précédentes, dans lequel le champ électrique axial généré par les électrodes auxiliaires est éliminé lors de la transmission d'ions à travers le dispositif de spectrométrie de mobilité différentielle fonctionnant dans un mode transmission dans lequel le filtrage de mobilité ionique est désactivé.
  5. Procédé selon la revendication 4, dans lequel l'élimination du champ électrique axial comprend l'ajustement du potentiel CC appliqué aux électrodes auxiliaires pour qu'il soit sensiblement identique à un décalage CC des tiges quadripolaires du guide d'ions ; ou
    comprenant en outre l'ajustement d'un potentiel sur une lentille (150a) adjacente à l'extrémité de sortie du guide d'ions pour que la lentille soit plus attractive pour les ions par rapport à un décalage de l'ensemble de tiges quadripolaires du guide d'ions.
  6. Procédé selon l'une quelconque des revendications précédentes, dans lequel l'ensemble de tiges multipolaires est un ensemble de tiges quadripolaires.
  7. Procédé selon l'une quelconque des revendications 1 à 5, dans lequel l'ensemble de tiges multipolaires comprend une première paire de tiges (244a, c) et une seconde paire de tiges (244b, d) pour former un ensemble de tiges quadripolaires et dans lequel les tiges de l'ensemble de tiges quadripolaires sont espacées de l'axe longitudinal pour que les tiges de chaque paire soient disposées sur des côtés opposés de l'axe longitudinal, et
    dans lequel la pluralité d'électrodes auxiliaires comprend au moins une paire d'électrodes auxiliaires s'étendant le long de l'axe longitudinal sur des côtés opposés de celui-ci, dans lequel chacune des électrodes auxiliaires est interposée entre une seule tige de la première paire de tiges et une seule tige de la seconde paire de tiges.
  8. Procédé selon l'une quelconque des revendications précédentes, dans lequel les électrodes auxiliaires ont une forme en T en coupe transversale.
  9. Système (100) de spectromètre de masse, comprenant :
    un dispositif de spectrométrie de mobilité différentielle (132), dans lequel, lorsqu'il est activé, le dispositif de spectrométrie de mobilité différentielle est configuré pour séparer des ions sur la base de leurs mobilités différentielles ;
    un guide (142, 242) d'ions configuré pour recevoir des ions provenant du dispositif de spectrométrie de mobilité différentielle, dans lequel le guide d'ions comprend un ensemble de tiges multipolaires (144) s'étendant le long d'un axe longitudinal depuis une extrémité d'entrée (140b) jusqu'à une extrémité de sortie (150b) ; et
    un système de commande (180) couplé de manière fonctionnelle au dispositif de spectrométrie de mobilité différentielle et au guide d'ions, le système de commande étant configuré pour :
    provoquer l'application d'une première combinaison de tension de séparation et de tension de compensation au dispositif de spectrométrie de mobilité différentielle de manière à transmettre une première pluralité d'ions ; et
    provoquer l'application d'une seconde combinaison de tension de séparation et de tension de compensation au dispositif de spectrométrie de mobilité différentielle de manière à transmettre une seconde pluralité d'ions, dans lequel au moins l'une parmi la tension de séparation et la tension de compensation de la seconde combinaison diffère de la tension de séparation et de la tension de compensation de la seconde combinaison ;
    caractérisé en ce que :
    le guide d'ions comprend en outre une pluralité d'électrodes auxiliaires (246a-d) ; et
    le système de commande est en outre configuré pour provoquer l'application d'une tension CC aux électrodes auxiliaires tout en transmettant la première et la seconde pluralité d'ions à travers le guide d'ions de manière à générer un champ électrique axial le long d'un axe longitudinal du guide d'ions.
  10. Système de spectrométrie de masse selon la revendication 9, dans lequel une durée entre la fin de la transmission de la première pluralité d'ions et l'initiation de la transmission de la seconde pluralité d'ions est inférieure à environ 30 ms, facultativement inférieure à environ 10 ms ; et/ou
    dans lequel le guide d'ions est disposé dans une chambre à vide ayant une pression dans la plage des mTorr.
  11. Système de spectrométrie de masse selon la revendication 9 ou la revendication 10, dans lequel le système de commande est en outre configuré pour :
    amener le dispositif de spectrométrie de mobilité différentielle à fonctionner dans un mode transmission dans lequel le filtrage de mobilité ionique est désactivé ; et
    ajuster la tension CC appliquée aux électrodes auxiliaires lors du fonctionnement en mode transmission pour éliminer le champ électrique axial généré par les électrodes auxiliaires ;
    dans lequel, facultativement, le système de commande est configuré pour ajuster la tension CC appliquée aux électrodes auxiliaires pour qu'elle soit sensiblement identique à un décalage CC des tiges multipolaires du guide d'ions lorsqu'il fonctionne en mode transmission.
  12. Système de spectrométrie de masse selon l'une quelconque des revendications 9 à 11, comprenant en outre une lentille (150a) disposée adjacente à l'extrémité de sortie du guide d'ions, dans lequel le système de commande est configuré pour ajuster un potentiel sur une lentille pour que la lentille soit plus attractive pour les ions par rapport à un décalage de l'ensemble de tiges multipolaires du guide d'ions.
  13. Système de spectrométrie de masse selon l'une quelconque des revendications 9 à 12, dans lequel l'ensemble de tiges multipolaires est un ensemble de tiges quadripolaires.
  14. Système de spectrométrie de masse selon l'une quelconque des revendications 9 à 12, dans lequel l'ensemble de tiges multipolaires comprend un ensemble de tiges quadripolaires comprenant une première paire de tiges (244a, c) et une seconde paire de tiges (244b, d) et dans lequel les tiges de l'ensemble de tiges quadripolaires sont espacées de l'axe longitudinal pour que les tiges de chaque paire soient disposées sur des côtés opposés de l'axe longitudinal, et
    dans lequel la pluralité d'électrodes auxiliaires comprend une paire d'électrodes auxiliaires s'étendant le long de l'axe longitudinal sur des côtés opposés de celui-ci, dans lequel chacune des électrodes auxiliaires est interposée entre une seule tige de la première paire de tiges et une seule tige de la seconde paire de tiges.
  15. Système de spectrométrie de masse selon l'une quelconque des revendications 9 à 14, dans lequel une distance entre une surface la plus interne des électrodes auxiliaires et l'axe longitudinal du guide d'ions diminue le long de la longueur du guide d'ions ; ou
    dans lequel les électrodes auxiliaires ont une forme en T en coupe transversale.
EP22829868.3A 2021-12-21 2022-12-13 Procédé et systèmes pour l'analyse d'ions à l'aide d'une spectrométrie de mobilité différentielle et d'un guide d'ions comprenant des électrodes auxiliaires supplémentaires Active EP4453554B1 (fr)

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WO2008068515A2 (fr) * 2006-12-08 2008-06-12 Micromass Uk Limited Spectromètre de masse
CA2720244C (fr) 2008-05-30 2018-02-27 Dh Technologies Development Pte. Ltd. Procede et systeme pour interface spectrometre de masse/spectrometre de mobilite differentielle actionnee par la depression avec resolution et selectivite ajustables
US20100282966A1 (en) 2008-05-30 2010-11-11 DH Technologies Development Pte Ltd. Method and system for vacuum driven mass spectrometer interface with adjustable resolution and selectivity
US20140353491A1 (en) * 2011-12-30 2014-12-04 DH Technologies Development Pte,Ltd. Creating an ion-ion reaction region within a low-pressure linear ion trap
JP6549130B2 (ja) 2013-12-31 2019-07-24 ディーエイチ テクノロジーズ デベロップメント プライベート リミテッド 微分移動度分光計のための噴射注入器入口
WO2021156775A1 (fr) * 2020-02-03 2021-08-12 Dh Technologies Development Pte. Ltd. Systèmes et procédés de séparation de composés de masse similaire par spectrométrie de mobilité différentielle
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